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FDA Grants Dapagliflozin Label Expansion for Treatment of Full Spectrum of Heart Failure


The label expansion is based on findings from the pivotal phase 3 DELIVER trial in which dapagliflozin reduced the composite CV/HF endpoint in HF patients with HFmrEF or HFpEF.

Dapagliflozin Wins Label Expansion for Treatment of Full Spectrum of Heart Failure  fda approval stamp  ©Waldenmarus/stock.adobe.com

The US Food and Drug Administration (FDA) recently approved a label expansion for dapagliflozin (Farxiga, AstraZeneca), the sodium glucose contransporter-2 (SGLT-2) inhibitor now indicated for reducing risk of cardiovascular (CV) death, hospitalization for heart failure (hHF), and urgent HF visits in adults with HF across the full range of ejection fraction, according to an AstraZeneca announcement.

Dapagliflozin was previously approved in the US for adults with HF with reduced ejection fraction (HFrEF).

“Approximately half of heart failure patients die within five years of diagnosis, highlighting an urgent unmet need for well-tolerated treatment options that can bring life-saving benefits and reduce the risk of cardiovascular death," said Ruud Dobber, executive vice-president of the BioPharmaceuticals Business Unit at AstraZeneca, in the company statement. "The approval of Farxiga in the US...will help patients across the full spectrum of heart failure lead healthier lives.”

Dapagliflozin, originally approved in 2014 in the US for treatment of hyperglycemia in type 2 diabetes (T2D), was in 2020 the first SGLT-2 inhibitor approved by the FDA for reducing the risk of CV death and hHF in patients with HFrEF, regardless of diabetes status. In 2021, dapagliflozin won FDA approval for reducing the risk of progression of chronic kidney disease (CKD), again regardless of T2D status. As a class, the SGLT-2 inhibitors continue to prove their pluripotency and have been incorporated into professional society guidelines on management of heart failure as well as of CKD.

Pivotal phase 3 clinical trial

The FDA's approved expansion of the dapagliflozin label is based on results of the pivotal phase 3 DELIVER trial (n=6263), designed to evaluate efficacy of once daily dapagliflozin 10 mg vs placebo in treatment of patients with LVEF >40%, with or without T2D. The study's primary composite endpoint was the time to first occurrence of CV death, hHF, or an urgent HF visit. The results, published in the New England Journal of Medicine, showed dapagliflozin reached a statistically significant and clinically meaningful early reduction of 18% in the primary composite endpoint of CV death or worsening HF in patients with HFmrEF or HFpEF. In analyses stratified by EF, DELIVER investigators found similar results among patients with LVEF of ≥60% and with LVEF <60%.

In a prespecified analysis of pooled data from the DELIVER and DAPA-HF clinical trials, published in Nature Medicine, researchers similarly found that dapagliflozin reduced risk for all assessed outcomes, including CV death, all-cause death, and total HF hospitalizations, in patients with HF regardless of EF. Findings from the pooled analysis represented the first SGLT-2 inhibitor to demonstrate a mortality benefit, according to AstraZeneca.

“The most recent guidelines of the American Heart Association, American College of Cardiology, and Heart Failure Society of America designated SGLT2 inhibitors as class IIA, level B, for the treatment of heart failure with a mildly reduced or preserved left ventricular ejection fraction,” wrote DELIVER investigators in the New England Journal of Medicine. “The results of the DELIVER trial may inform future guidelines and provide further guidance for their broader use in clinical practice.”

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